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DOI: 10.1201/9781003336433-8

8

Theoretical Biophysics

Computational Biophysical Tools and

Methods that Require a Pencil and Paper

It is nice to know that the computer understands the problem. But I would like to understand

it too.

—​Nobel laureate Eugene Wigner (1902–​1995), one of the founders

of modern quantum mechanics

General Idea: The increase in computational power and efficiency has transformed biophysics

in permitting many biological questions to be tackled largely inside multicore computers. In

this chapter, we discuss the development and application of several such in silico techniques,

many of which benefit from computing that can be spatially delocalized both in terms of the

servers running the algorithms and those manipulating and archiving significant amounts of

data. However, there are also many challenging biological questions that can be tackled with

theoretical biophysical tools consisting of a pencil and a piece of paper.

8.1  INTRODUCTION

Previously in this book we have discussed a range of valuable biophysical tools and techniques

that can be used primarily in experimental investigations. However, biological insight from any

experiment demands not only the right hardware but also a range of appropriate techniques

that can, rather broadly, be described as theoretical biophysics. Ultimately, genuine insight

into the operation of complex processes in biology is only gleaned by constructing a theoret­

ical model of some sort. But this is a subtle point on which some life and physical scientists

differ in their interpretation. To some biologists, a “model” is synonymous with specula­

tion toward explaining experimental observations, embodied in a hypothesis. However, to

many physical scientists, a “model” is a real structure built from sound physical and math­

ematical principles that can be tested robustly against the experimental data obtained, in our

case from the vast armory of biophysical experimental techniques described in Chapters 3

through 7 in particular.

Theoretical biophysics methods are either directly coupled to the experiments through

analyzing the results of specific experimental investigations or can be used to generate fal­

sifiable predictions or simulate the physical processes of a particular biological system. This

predictive capability is absolutely key to establishing a valuable theoretical biophysics frame­

work, which is one that in essence contains more summed information than was used in its

own construction, in other words, a model that goes beyond simply redefining/​renaming

physical parameters, but instead tells us something useful.

The challenges with theoretical biophysics techniques are coupled with the length and

time scales of the biological processes under investigation. In this chapter, we consider

regimes that extend from femtosecond fluctuations at the level of atomistic effects, up to the

time scales of several seconds at the length scale of rigid body models of whole organisms.